ResearchBasic science: ObstetricsEffects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia
Section snippets
Animals
The study was approved and registered by the Committee of Animal Investigations (CINVA 220) at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF. During all the steps of the study, the animals were cared for according to the Mexican official norm NOM-062-ZOO-1999 Specifications Techniques of Reproduction, Care, and Use of Laboratory Animals.
Forty-three short-haired multiparous female, pigmented guinea pigs (Cavia porcellus) were housed for 5 days in a harem
Results
At 35 days of gestation, when pregnancy was confirmed and animals were randomly allocated to a treatment, the weight of the mothers was approximately 0.7 kg in all 3 study groups (P = .6) (Table 1). At term, the animals in the 3 study groups had increased their body weight by approximately 0.3 kg (P = .4). In contrast, the guinea piglets born to mothers treated with sildenafil 500 μg/kg were 1.5 times heavier and significantly larger than piglets born to either of the other 2 groups (Table 1).
Comment
Our study shows that, in guinea pigs, the offspring born to mothers treated with sildenafil have an increased survival rate to intrapartum asphyxia. Pulmonary arterial vasoconstriction occurs as a response to hypoxia, inducing a sustained elevation in the pulmonary blood pressures that causes pulmonary hypertension.10 The PDEs, mainly PDE5, are present in the pulmonary vascular smooth muscle,11 and PDE5 inhibitors including sildenafil have demonstrated to be effective in the pharmacological
Acknowledgments
The authors are grateful to Antonio Verduzco, DVM, for his help and training provided to investigators on the care and surgical procedures in the pregnant guinea pigs, and Ms Olivia Tischler for her valuable assistance in editing the manuscript. The study was not supported in any form by any pharmaceutical company.
References (29)
- et al.
Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes
J Urol
(1998) - et al.
Sildenafil, a type-5 cGMP phsphodiesterase inhibitor, specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro
J Urol
(1998) - et al.
Recent developments in the pathophysiology and treatment of persistent pulmonary hypertension of the newborn
J Pediatr
(1995) - et al.
Efficacy of sildenafil as a rescue therapy for patients with severe pulmonary arterial hypertension and given long-term treatment with prostanoids: 2-year experience
J Heart Lung Transplant
(2006) - et al.
Safety and efficacy of sildenafil therapy in children with pulmonary hypertension
Int J Cardiol
(2005) - et al.
Early developmental origins of impaired lung structure and function
Early Hum Dev
(2005) - et al.
Intra-uterine transmission of disease
Placenta
(2003) - et al.
Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide
Circulation
(2002) - et al.
Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension
Am J Respir Crit Care Med
(2002) - et al.
The cGMP-specific phosphodiesterase inhibitor E4021 dilates the pulmonary circulation
Am J Respir Crit Care Med
(1999)
Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus
Am J Physiol Lung Cell Mol Physiol
Sildenafil administration during pregnancy increases fetal rat weight gain
FASEB J
Sildenafil citrate and fetal outcome in pregnant rats
Fetal Diagn Ther
Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine
Obstet Gynecol
Cited by (28)
The impact of prenatal environment on postnatal life and performance: Future perspectives for prevention and treatment
2020, TheriogenologyCitation Excerpt :In this sense, sildenafil citrate (commonly known by its brand name Viagra®) is a selective inhibitor of phosphodiesterase type 5 (PDE-5), which prevents the hydrolysis of cyclic guanosine monophosphate (cGMP), which acts as the biological signal for NO synthesis [25] and, therefore, increases NO bioavailability. Therefore, the use of sildenafil can help to optimize placental development and function and, thus, can help to avoid IUGR [26–29]. Observational studies in the case of the human species have shown promising results [30–34], but an experiment conducted by our group using rabbits as an experimental model has shown that maternal treatment with sildenafil can induce an excess of blood supply to the fetal brain and therefore fetal hypertension [29].
Maternal sildenafil for severe fetal growth restriction (STRIDER): a multicentre, randomised, placebo-controlled, double-blind trial
2018, The Lancet Child and Adolescent HealthCitation Excerpt :At present, we cannot offer a plausible pathophysiological explanation for the possible adverse effect of sildenafil on the fetal blood flow in our cohort. Our findings are in contrast with animal and several previously reported clinical studies.17–20,23–29 The sildenafil dose used in our study was based on the consensus from researchers with most experience in clinical evaluation of sildenafil in pregnancy at the time18,21 and a higher dose could possibly have been more effective.
Possible benefits and risks of polyphenols supplementation during pregnancy
2018, Polyphenols: Mechanisms of Action in Human Health and DiseaseEvaluation of the protective effect of thiamine pyrophosphate based on the biochemical analysis of rabbit foetuses at 30 days of gestation
2016, Reproductive ToxicologyCitation Excerpt :In our study, the group without PPT presented pCO2 levels of approximately 112 mmHg at 0 min, which remained unchanged after the onset of the induced ischaemia. These data concur with those reported by Sánchez-Aparicio [6], who found a tendency towards an increase in pCO2 levels in guinea pig foetuses before, and at 5 min after, occlusion of the umbilical cord (75.9 ± 19.3 vs. 87 ± 22.9 mmHg, respectively). In our results, however, after 45 min of ischaemia, pCO2 levels decreased by 89% to approximately 22 mmHg.
Review: Potential druggable targets for the treatment of early onset preeclampsia
2013, Pregnancy HypertensionVetrabutine clorhydrate use in dystocic farrowings minimizes hemodynamic sequels in piglets
2012, TheriogenologyCitation Excerpt :Parturition is a critical event in polytocous species [1–4].
Cite this article as: Sánchez-Aparicio P, Mota-Rojas D, Nava-Ocampo AA, et al. Effects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia. Am J Obstet Gynecol 2008;198:127.e1-127.e6.
Reprints not available from the authors.
The study was supported by grant UAM-PTC-028 from the Programa de Mejoramiento del Profesorado to the Cuerpo Académico de Etología, Producción Porcina y Fauna Silvestre, Universidad Autónoma Metropolitana, and the Sistema Nacional de Investigadores (to D.M.-R. M.E.T.-O., A.A.-R., E.A., and M.A.-S.). This study was part of the MSc thesis of P.S.-A., who was supported by grant 193059 from CONACYT at the Maestría en Ciencias de la Producción y de la Salud Animal, Universidad Nacional Autónoma de México.